rs2069952

Variant names:

• chr20-35176148-C-T
• rs2069952
• NM_006404.5:c.323-20C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006404.5(PROCR):​c.323-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,610,778 control chromosomes in the GnomAD database, including 267,278 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (30044 hom., cov: 31)
  • Exomes 𝑓: 0.57 (237234 hom.)
• Consequence: PROCR NM_006404.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 37 publications found

Genes affected

PROCR (HGNC:9452): (protein C receptor) The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. Mutations in this gene have been associated with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. The encoded protein may also play a role in malarial infection and has been associated with cancer. [provided by RefSeq, Jul 2013]

MMP24-AS1-EDEM2 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROCR	NM_006404.5	c.323-20C>T		intron_variant	Intron 2 of 3	ENST00000216968.5	NP_006395.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROCR	ENST00000216968.5	c.323-20C>T		intron_variant	Intron 2 of 3	1	NM_006404.5	ENSP00000216968.3
PROCR	ENST00000635377.1	c.221-20C>T		intron_variant	Intron 1 of 3	5		ENSP00000489117.1
PROCR	ENST00000634509.1	c.-205C>T		upstream_gene_variant		3		ENSP00000489456.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93443 AN: 151842 Hom.: 29989 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.580

GnomAD2 exomes AF: 0.555 AC: 138199 AN: 249030 AF XY: 0.564

Gnomad AFR exome AF: 0.811

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.372

Gnomad FIN exome AF: 0.575

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.565 AC: 824342 AN: 1458818 Hom.: 237234 Cov.: 47 AF XY: 0.568 AC XY: 412507 AN XY: 725928

African (AFR) AF: 0.818 AC: 27319 AN: 33390

American (AMR) AF: 0.374 AC: 16700 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 15662 AN: 26118

East Asian (EAS) AF: 0.322 AC: 12783 AN: 39692

South Asian (SAS) AF: 0.677 AC: 58334 AN: 86188

European-Finnish (FIN) AF: 0.573 AC: 30468 AN: 53212

Middle Eastern (MID) AF: 0.593 AC: 3418 AN: 5764

European-Non Finnish (NFE) AF: 0.563 AC: 625008 AN: 1109430

Other (OTH) AF: 0.575 AC: 34650 AN: 60312

GnomAD4 genome AF: 0.616 AC: 93553 AN: 151960 Hom.: 30044 Cov.: 31 AF XY: 0.615 AC XY: 45653 AN XY: 74266

African (AFR) AF: 0.803 AC: 33297 AN: 41454

American (AMR) AF: 0.485 AC: 7390 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2080 AN: 3472

East Asian (EAS) AF: 0.358 AC: 1843 AN: 5144

South Asian (SAS) AF: 0.670 AC: 3227 AN: 4816

European-Finnish (FIN) AF: 0.569 AC: 6012 AN: 10566

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37872 AN: 67946

Other (OTH) AF: 0.585 AC: 1236 AN: 2112

Alfa AF: 0.628 Hom.: 11833

Bravo AF: 0.609

Asia WGS AF: 0.579 AC: 2016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.26
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2069952; hg19: chr20-33763951; COSMIC: COSV53826106; COSMIC: COSV53826106;